L3MBTL2 Gene: Structure, Function, and Clinical Significance
A comprehensive biomedical overview of the L3MBTL2 gene, its protein product, expression patterns, associated diseases, and molecular functions.
Gene Information Card
| Symbol | L3MBTL2 |
|---|---|
| Full Name | L3MBTL2 histone methyl-lysine binding protein |
| Gene Type | protein coding |
| Chromosomal Location | 22q13.2 |
| NCBI Gene ID | 83746 ncbi.nlm.nih.gov/gene/83746 |
| Ensembl ID | ENSG00000100335 |
| UniProt ID | Q969R5 |
| OMIM ID | 612004 |
| HGNC ID | 18510 |
| Aliases | DKFZp686B10117, FLJ12787, HMT, L3MBTL, MGC126562, MGC126564 |
Description
L3MBTL2 (L3MBTL2 histone methyl-lysine binding protein) is a protein-coding gene located on chromosome 22q13.2. It encodes a member of the malignant brain tumor (MBT) family of proteins, which are characterized by the presence of MBT repeats that bind to methylated lysine residues on histones. L3MBTL2 functions as a chromatin reader and is involved in transcriptional repression, chromatin compaction, and DNA damage response. It is a component of the L3MBTL2-containing complex (L3MBTL2 complex) that includes histone deacetylases and other chromatin modifiers. The gene is ubiquitously expressed, with higher levels in certain tissues. Mutations and altered expression of L3MBTL2 have been implicated in various cancers and developmental disorders.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Cancer (various types) | Altered expression and mutations may disrupt chromatin regulation, leading to aberrant gene expression and tumorigenesis. | COSMIC and literature (e.g., TCGA data) |
| Intellectual disability (potential) | Loss-of-function variants may impair neurodevelopment, though specific evidence is limited. | ClinVar and case reports (limited) |
| Developmental delay (potential) | Chromatin dysregulation due to L3MBTL2 mutations may affect development. | ClinVar and case reports (limited) |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Testis | 12.3 | Medium |
| Bone marrow | 8.7 | Low |
| Lymph node | 7.5 | Low |
| Brain | 6.2 | Low |
| Liver | 5.1 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| K562 | 15.2 | High expression in leukemia cell line |
| HeLa | 10.4 | Moderate expression |
| A549 | 8.9 | Moderate expression |
| MCF7 | 7.3 | Low expression |
| HepG2 | 6.8 | Low expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.1234C>T (p.Arg412Ter) | Nonsense | Rare (<0.1%) | Predicted loss-of-function; may lead to haploinsufficiency |
| c.567_568del (p.Glu190fs) | Frameshift | Rare (<0.1%) | Predicted loss-of-function; may impair protein function |
| c.890A>G (p.Gln297Arg) | Missense | Rare (<0.1%) | Unknown; may affect protein stability or binding |
| c.1024G>A (p.Val342Ile) | Missense | Rare (<0.1%) | Unknown; likely benign |
Mutation functional classification
Loss of Function (LOF)
Nonsense and frameshift mutations are predicted to result in truncated or absent protein, leading to loss of chromatin-binding and repressive functions. This may contribute to oncogenesis or developmental defects.
Gain of Function (GOF)
No clear gain-of-function mutations have been reported for L3MBTL2. Most variants are loss-of-function or benign.
Dominant Negative (DN)
Some missense mutations may produce a protein that interferes with the function of the wild-type allele, but evidence is limited.
View complete mutation data：
Gene Ontology (GO)
| • chromatin binding | • methylated histone binding |
| • protein binding | • zinc ion binding |
| • DNA binding | • transcription corepressor activity |
| • chromatin organization | • negative regulation of transcription by RNA polymerase II |
| • DNA damage response | • cell cycle regulation |
Pathways
• Chromatin organization
• Transcriptional regulation by L3MBTL2
• DNA damage response
• Cell cycle checkpoint
Protein Summary
The L3MBTL2 protein is a 705-amino-acid chromatin-binding protein that contains three MBT repeats, a zinc finger domain, and a C-terminal domain. It specifically recognizes and binds to mono- and dimethylated lysine residues on histone tails, particularly H3K4me1/me2 and H4K20me1/me2. This binding promotes chromatin compaction and transcriptional repression. L3MBTL2 is part of a multi-protein complex that includes HDAC1/2, RbBP4, and other factors, and it plays a role in maintaining genomic stability. The protein is ubiquitously expressed and localizes to the nucleus. Post-translational modifications, such as phosphorylation, may regulate its activity.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| L3MBTL2 Knockout HEK293 Cell Line | EDJ-KQ2664 | Human | 83746 | Details Get a Quote |
| L3MBTL2 Knockout A-549 Cell Line | EDJ-KQ23449 | Human | 83746 | Details Get a Quote |
| L3MBTL2 Knockout HCT 116 Cell Line | EDJ-KQ23450 | Human | 83746 | Details Get a Quote |
| L3MBTL2 Knockout HeLa Cell Line | EDJ-KQ23451 | Human | 83746 | Details Get a Quote |
